Characterization of focal liver lesions with SonoVue®-enhanced sonography: International multicenter-study in comparison to CT and MRI

Table 1 US equipment and contrast-specific modes

Equipment manufacturer	Scanning mode	No. of patients scanned	Transducer	Mechanical index
Elegra, Siemens	Ensemble contrast imaging (ECI)	25	Convex array	0.10-0.30
			3.5C40H
Aplio, Toshiba	Contrast tissue discrimination (CTD)	24	Convex array	0.1
			PVT375AT
HDI 5000, Philips	Pulse inversion harmonic contrast imaging (PI)	18	Convex array	0.04-0.12
			C5-2
Technos MPX, Esaote	Contrast tuned imaging (CnTI)	18	Convex array	0.09-0.10
			CA430
Logic 9, GE	Coded phase inversion (PI)	16	Convex array	0.09-0.17
			3.5C
SSD-5500, Aloka	Extended pure harmonic detection (E-PHD)	16	Convex array	0.09-0.20
			UST 9126
Sequoia, Siemens	Cadence contrast pulse sequencing (CPS)	7	Convex array	0.15-0.24
			4C1-S
IU 22, Philips	Pulse inversion (PI)	3	Convex array	0.06-0.07
			C5-2

Table 2 Classification and diagnostic criteria for the assessment of focal liver lesions

Lesion type	Arterial phase	Portal venous phase	Sinusoidal phase
Malignant lesions
Hepatocellular carcinoma (HCC)	Hyperenhanced, often with prominent delineation of feeding vessels around and inside of the lesion, however in well differentiated tumors sometimes only weak arterial enhancement	Iso- or hypoenhanced, usually rapid contrast wash-out	Mostly hypoenhanced, however in well differentiated tumors some portal venous enhancement may be present
Cholangiocarcinoma (CCC)	Moderately hyperenhanced	Iso- or hypoenhanced	Mostly hypoenhanced
Hypervascular metastases (MET)	Hyperenhanced, often restricted to the margin of the lesion	Iso- or hypoenhanced	Always hypoenhanced (black spots)
Hypovascular metastases (MET)	Not enhanced or only few isolated spots inside of the lesion	Hypoenhanced	Always hypoenhanced (black spots)
Other malignant
Benign lesions
Hemangioma (typical)	Peripheral nodular enhancement, sharp margin in high-flow hemangiomas: complete filling of the lesion during arterial phase	Slow centripetal progression of the enhancement (‘iris diaphragm sign’), leading to an iso- or hyperenhancedappearance; fill-in can be very slowly (lasting minutes) or rather fast (lasting less than a minute)	More or less complete enhancement, prolonged compared to surrounding liver tissue and therefore hyperenhanced at later time points; enhancement may be incomplete in case of (partial) thrombosis
Hemangioma (atypical)	Peripheral nodular enhancement, sharp margin or no enhancement (complete thrombosis) or complete enhancement (high flow hemangioma)	Slow centripetal progression of the enhancement (‘iris diaphragm sign’), leading to an iso- or hyperenhanced appearance; fill-in can be very slowly (lasting minutes) or rather fast (lasting less than a minute)	More or less complete enhancement, prolonged compared to surrounding liver tissue and therefore hyperenhanced at later time points; enhancement may be incomplete in case of (partial) thrombosis
Focal nodular hyperplasia (FNH)	Hyperenhanced, with fast centrifugal filling of the lesion; usually a central vessel and radial vascular branches can be delineated, especially in larger lesions (‘spoke and wheel sign’)	Iso- or hyperenhanced	Iso- or hyperenhanced, central scar may become visible
Hepatic adenoma	Hyperenhanced, frequently with fast centrifugal filling and rapid contrast wash-out; no radial vascular structures visible	Iso- or hyperenhanced; hypoenhanced areas in case of central bleeding or scar	Iso- or hyperenhanced; hypoenhanced areas in case of central bleeding or scar; no central scar or radial intralesional structures
Large regenerating or dysplastic nodules	Isoenhanced	Isoenhanced	Isoenhanced
Focal fatty accumulation	Isoenhanced	Isoenhanced	Isoenhanced
Focal fatty sparing	Isoenhanced	Isoenhanced	Isoenhanced
Cyst	No enhancement	No enhancement	No enhancement
Other benign

Table 3 Lesion character of target lesion: SonoVue®-enhanced sonography vs other imaging modalities and final reference diagnosis n (%)

	Unenhanced sonography	SonoVue®-enhanced sonography	CT and/or MRI	Histology	Final reference diagnosis
n	127	127	115	31	127
Benign	25 (19.7)	61 (48.0)	41 (35.7)	8 (25.8)	68 (53.5)
Hemangioma (typical)	10 (40.0)	11 (18.0)	12 (29.3)	1 (12.5)	10 (14.7)
Hemangioma (atypical)	5 (20.0)	16 (26.2)	12 (29.3)	1 (12.5)	19 (27.9)
Focal nodular hyperplasia	6 (24.0)	20 (32.8)	9 (22.0)	3 (37.5)	24 (35.3)
Hepatic adenoma	0	2 (3.3)	2 (4.9)	2 (25.0)	3 (4.4)
Regenerating or dysplastic nodules	1 (4.0)	2 (3.3)	1 (2.4)	0	2 (2.9)
Focal fatty accumulation	0	2 (3.3)	1 (2.4)	0	2 (2.9)
Focal fatty sparing	2 (8.0)	3 (5.0)	1 (2.4)	0	3 (4.4)
Cyst	0	0	0	0	0
Other benign	1 (4.0)	5 (8.2)	3 (7.3)	1 (12.5)	5 (7.4)
Malignant	25 (19.7)	57 (44.9)	38 (33.0)	21 (67.7)	55 (43.3)
Hepatocellular carcinoma	14 (56.0)	34 (59.7)	21 (55.3)	13 (61.9)	33 (60.0)
Cholangiocarcinoma	0	0	0	1 (4.8)	1 (1.8)
Hypervascular metastasis	2 (8.0)	9 (15.8)	4 (10.5)	2 (9.5)	7 (12.7)
Hypovascular metastasis	9 (36.0)	10 (17.5)	10 (26.3)	3 (14.3)	10 (18.2)
Other malignant lesion	0	4 (7.0)	3 (7.9)	2 (9.5)	4 (7.3)
Indeterminate	77 (60.6)	9 (7.1)	34 (29.6)	2 (6.5)	4 (3.2)

CT: Computed tomography; MRI: Magnetic resonance imaging.